The objectives of this program are to verify two hypotheses. First, the quantifiable differences in surface reactivity of nanoparticles, as measured by acidity, redox chemistry, metal ion binding and Fenton chemistry as compared to micron-sized particles of similar composition cannot be explained by the increase in surface area alone. Second, the oxidative stress and inflammatory response induced by nanoparticles upon interaction with macrophages and epithelial cells is dependent on their surface reactivity. The basis of these hypotheses is that nanoparticles contain significantly higher number of "broken" bonds on the surface that provide different reactivity as compared to larger particles. The experimental approach focuses on three classes of manufactured nanoparticles, catalysts (aluminosilicates), titania and carbon. For the catalysts and titania samples, nanoparticles (< 100 nm) and micron-sized particles of similar bulk composition will be studied. For carbon, carbon black and single walled carbon nanotubes are chosen. Nanoparticles of aluminosilicates and titania will be synthesized, whereas the other particles will be obtained from commercial sources. Characterization will involve electron microscopy, surface area, surface and bulk composition. Reactivity of well- characterized particles in regards to their acidity, reaction with antioxidants simulating the lung lining fluid, coordination of iron and Fenton chemistry will be carried out using spectroscopic methods. Particular attention will be paid to surface activation as may exist during manufacturing and processing. In-vitro oxidative stress and inflammatory responses upon phagocytosis of the particles by macrophages and pulmonary epithelial cells will form the toxicological/biological end points of the study. Methods include gene array techniques, assays for reactive oxygen species and adhesion molecules on endothelial cells. As nanotechnology advances are made over the next decades, exposure to nanoparticles is going to increase significantly. Potential inhalation risks exist during manufacture, product recovery, processing and in some cases during consumer use. Risk assessment and management will be facilitated if broad generalizations can be developed correlating surface structure and reactivity of nanoparticles, much like we classify molecules and their toxicity. The expected results from this project will examine for the first time how unsaturated bonds on nanoparticles influence their chemical and biological reactivity. Preparation of nanoparticles in an activated state with unpassivated surface atoms is an important part of this research program. [unreadable] [unreadable] [unreadable] [unreadable]